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Familial Cancer Variant Prioritization Pipeline version 2 (FCVPPv2) applied to a papillary thyroid cancer family

Kumar, Abhishek; Bandapalli, Obul Reddy; Paramasivam, Nagarajan; Giangiobbe, Sara; Diquigiovanni, Chiara; Bonora, Elena; Eils, Roland; Schlesner, Matthias; Hemminki, Kari LU and Försti, Asta LU (2018) In Scientific Reports 8(1).
Abstract

Whole-genome sequencing methods in familial cancer are useful to unravel rare clinically important cancer predisposing variants. Here, we present improvements in our pedigree-based familial cancer variant prioritization pipeline referred as FCVPPv2, including 12 tools for evaluating deleteriousness and 5 intolerance scores for missense variants. This pipeline is also capable of assessing non-coding regions by combining FANTOM5 data with sets of tools like Bedtools, ChromHMM, Miranda, SNPnexus and Targetscan. We tested this pipeline in a family with history of a papillary thyroid cancer. Only one variant causing an amino acid change G573R (dbSNP ID rs145736623, NM_019609.4:exon11:c.G1717A:p.G573R) in the carboxypeptidase gene CPXM1... (More)

Whole-genome sequencing methods in familial cancer are useful to unravel rare clinically important cancer predisposing variants. Here, we present improvements in our pedigree-based familial cancer variant prioritization pipeline referred as FCVPPv2, including 12 tools for evaluating deleteriousness and 5 intolerance scores for missense variants. This pipeline is also capable of assessing non-coding regions by combining FANTOM5 data with sets of tools like Bedtools, ChromHMM, Miranda, SNPnexus and Targetscan. We tested this pipeline in a family with history of a papillary thyroid cancer. Only one variant causing an amino acid change G573R (dbSNP ID rs145736623, NM_019609.4:exon11:c.G1717A:p.G573R) in the carboxypeptidase gene CPXM1 survived our pipeline. This variant is located in a highly conserved region across vertebrates in the peptidase_M14 domain (Pfam ID PF00246). The CPXM1 gene may be involved in adipogenesis and extracellular matrix remodelling and it has been suggested to be a tumour suppressor in breast cancer. However, the presence of the variant in the ExAC database suggests it to be a rare polymorphism or a low-penetrance risk allele. Overall, our pipeline is a comprehensive approach for prediction of predisposing variants for high-risk cancer families, for which a functional characterization is a crucial step to confirm their role in cancer predisposition.

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organization
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publication status
published
subject
in
Scientific Reports
volume
8
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85051083154
ISSN
2045-2322
DOI
10.1038/s41598-018-29952-z
language
English
LU publication?
yes
id
81a693c9-13fb-4300-b99b-5fe1cfc69ecb
date added to LUP
2018-08-14 13:25:09
date last changed
2019-11-13 05:13:01
@article{81a693c9-13fb-4300-b99b-5fe1cfc69ecb,
  abstract     = {<p>Whole-genome sequencing methods in familial cancer are useful to unravel rare clinically important cancer predisposing variants. Here, we present improvements in our pedigree-based familial cancer variant prioritization pipeline referred as FCVPPv2, including 12 tools for evaluating deleteriousness and 5 intolerance scores for missense variants. This pipeline is also capable of assessing non-coding regions by combining FANTOM5 data with sets of tools like Bedtools, ChromHMM, Miranda, SNPnexus and Targetscan. We tested this pipeline in a family with history of a papillary thyroid cancer. Only one variant causing an amino acid change G573R (dbSNP ID rs145736623, NM_019609.4:exon11:c.G1717A:p.G573R) in the carboxypeptidase gene CPXM1 survived our pipeline. This variant is located in a highly conserved region across vertebrates in the peptidase_M14 domain (Pfam ID PF00246). The CPXM1 gene may be involved in adipogenesis and extracellular matrix remodelling and it has been suggested to be a tumour suppressor in breast cancer. However, the presence of the variant in the ExAC database suggests it to be a rare polymorphism or a low-penetrance risk allele. Overall, our pipeline is a comprehensive approach for prediction of predisposing variants for high-risk cancer families, for which a functional characterization is a crucial step to confirm their role in cancer predisposition.</p>},
  articleno    = {11635},
  author       = {Kumar, Abhishek and Bandapalli, Obul Reddy and Paramasivam, Nagarajan and Giangiobbe, Sara and Diquigiovanni, Chiara and Bonora, Elena and Eils, Roland and Schlesner, Matthias and Hemminki, Kari and Försti, Asta},
  issn         = {2045-2322},
  language     = {eng},
  month        = {08},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Familial Cancer Variant Prioritization Pipeline version 2 (FCVPPv2) applied to a papillary thyroid cancer family},
  url          = {http://dx.doi.org/10.1038/s41598-018-29952-z},
  volume       = {8},
  year         = {2018},
}